Glial Cell Line-derived Neurotrophic Factor (GDNF)

Glial-cell-line-derived neurotrophic factor (GDNF), a neurotrophic factor belongs to the GDNF family ligands (GFLs)., promotes survival of dopamine neurons. GDNF demonstrates a variety of neuroprotective roles for mammalian neurons. GDNF protein is widely distributed throughout both the central and peripheral nervous systems. Synthesis and secretion of GDNF occur in many cell types such as glial cells like astrocytes, oligodendrocytes, and Schwann cells; motor neurons (MNs); and skeletal muscle^[1].
GDNF is originally isolated from cultured B49 rat glial cells and found to enhance the survival and differentiation of dopaminergic neurons in primary cultures by promoting dopamine uptake. Similar to other members of the TGF-β superfamily, GDNF is first synthesized as a precursor protein (pro-GDNF). After a series of protein cleavage and processing, the 211 amino acid pro-GDNF is finally converted into the active and mature form of GDNF. GDNF has the ability to trigger receptor tyrosine kinase RET phosphorylation, whose downstream effects have been found to promote neuronal health and survival. The binding of GDNF to its receptors triggers several intracellular signaling pathways which play roles in promoting the development, survival, and maintenance of neuron-neuron and neuron-target tissue interactions. The synthesis and regulation of GDNF have been shown to be altered in many diseases, aging, exercise, and addiction. The neuroprotective effects of GDNF may be used to develop treatments and therapies to ameliorate neurodegenerative diseases such as amyotrophic lateral sclerosis (ALS). Intracerebral GDNF administration exerts both protective and reparative effects on the nigrostriatal dopamine system, which may have implications for the development of new treatment strategies for Parkinson's disease^[1][2].

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